Biomedical subjects
Publications and source records attributed to K Capek.
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Na,K-ATPase function was studied in order to evaluate the mechanism of increased colonic Na+ transport during early postnatal development. The maximum Na(+)-pumping activity that was represented by the equivalent short-circuit current after addition of nystatin (ISCN) did not change during postnatal life or after adrenalectomy performed in 16-day-old rats. ISCN was entirely inhibited by ouabain; the inhibitory constant was 0.1 mM in 10-day-old (young) and 0.4 mM in 90-day-old (adult) rats. The affinity of the Na,K pump for Na+ was higher in young (11 mM) than in adult animals (19 mM). The Na,K-ATPase activity (measured after unmasking of latent activity by treatment with sodium dodecylsulfate) increased during development and was also not influenced by adrenalectomy of 16-day-old rats. The inhibitory constant for ouabain (KI) was not changed during development (0.1-0.3 mM). Specific [3H]ouabain binding to isolated colonocytes increased during development (19 and 82 pmol/mg protein), the dissociation constant (KD) was 8 and 21 microM in young and adult rats, respectively. The Na+ turnover rate per single Na,K pump, which was calculated from ISCN and estimated density of binding sites per cm2 of tissue was 500 in adult and 6400 Na+/min.site in young rats. These data indicate that they very high Na+ transport during early postnatal life reflects an elevated turnover rate and increased affinity for Na+ of a single isoform of the Na,K pump. The development of Na+ extrusion across the basolateral membrane is not directly regulated by corticosteroids.
Alkaline hydrolysis of alpha-D-glucopyranosyl 3,4-anhydro-beta-D-ribo-hexulofuranoside (1) involves participation of HO-2 and leads to 2,3'-anhydrosucrose (2). The structure of 2 was assigned on the basis of the n.m.r. and mass spectra of its hexa-acetate 3 and confirmed by the formation from 2 of the 6,6'-di-(4) and 6,1',6'-tri-O-trityl (5) derivatives, the 4,6-O-isopropylidene derivative (6), and 2,3':3,4-dianhydro-galacto-sucrose, isolated as the tetra-acetate 7. The structure of 7 was confirmed by its conversion into the 4'-O-tosyl-6,1',6'-O-trityl derivative 14 and by unambiguous synthesis from 6.
Isolated cells from rat distal colon were investigated with the patch-clamp technique. In cell-attached and cell-excised patches (inside-out) single chloride channels with outward-rectifying properties were observed. In excised patches the single-channel conductance g was 47 +/- 5 pS at positive and 22 +/- 2 pS at negative clamp potentials (n = 6). The Cl- channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB, 10 microM) induced fast closing events, whereas 10 microM of 3',5-dichlorodiphenylamine-2-carboxylic acid (DCDPC) had no effect when applied to the cytosolic side. Quinine in the bath inhibited the Cl- channel by reducing its single-channel amplitude and increased open channel noise. With 0.1 mM the current amplitude decreased by 54% and with 1 mM quinine by 67%. Ca2(+)-dependent nonselective cation channels where observed after excision of the membrane patch. This channel was completely and reversibly inhibited by 100 microM DCDPC. Application of 1 mM quinine to the bath induced flickering and reduced the open-state probability from 0.94 to 0.44. In summary, besides its well established effects on K+ channels, quinine also inhibits nonselective cation channels and chloride channels by inducing fast closing events.
1. The influence of chronic forelimb immobilization enforcing movement in upright position on blood pressure was studied in monkeys. 2. In the course of 6 months all animals subjected to immobilization became hypertensive due to a parallel increase of systolic and diastolic pressure by about 30%. The hypertension was demonstrable both in awake and anaesthetized animals and persisted even after restitution of a normal movement regime. 3. In the chronic stage (after 15 months), the plasma renin concentration was decreased by 55%, indicating that the renin-angiotensin system activation does not participate in the maintenance of the hypertensive state. The plasma volume was diminished by 18%, while the interstitial fluid volume did not differ significantly from control values. 4. It is concluded that chronic forelimb immobilization in monkeys induces a low-renin hypertension, associated with changes in extracellular fluid compartments resembling the pattern found in the hypovolaemic type of essential hypertension.
To study the role of corticosteroids in the regulation of colonic electrogenic amiloride-sensitive Na+ absorption (ISCNa) and barium-sensitive K+ secretion (ISCK) during development, we investigated suckling (10-day old), weanling (25-day old) and adult (90-day old) adrenalectomized rats after they had received aldosterone, dexamethasone or corticosterone. Adrenalectomy reduced markedly ISCNa in suckling rats and completely inhibited ISCNa in weanling animals; the ISCNa was absent in intact adult rats. The doses of aldosterone, corticosterone and dexamethasone estimated to be equivalent to the endogenous production rate of aldosterone and corticosterone restored ISCNa after 1 day in both suckling and weanling rats. Compared with aldosterone, glucocorticoids produced a greater increase in ISCNa. Concurrent spironolactone treatment (a mineralocorticoid antagonist) completely prevented the effect of aldosterone but had no effect in dexamethasone-treated rats. The glucocorticoid antagonist RU 38 486 inhibited the dexamethasone-induction of ISCNa but had no effect on aldosterone. The response to corticosteroids, measured as the increase of ISCNa, declined from suckling to adult rats. In contrast to ISCNa, the same time of treatment and the same doses of corticosteroids did not influence ISCK. ISCK was stimulated only after chronic treatment (4 days). These findings suggest that, in the distal colon of young rats, (1) both corticosteroids may regulate amiloride-sensitive Na+ absorption and barium-sensitive K+ secretion, (2) different receptors mediate the colonic effects of glucocorticoids and mineralocorticoids, (3) immature rats are more sensitive to corticosteroids than adult animals, and (4) the acute effect of corticosteroids is an increase in Na+ absorption which is followed by delayed stimulation of K+ secretion.
To evaluate developmental changes in colonic sodium transport, the sensitivity of the transepithelial potential and short-circuit current to amiloride was investigated. The amiloride-sensitive short-circuit current (IscNa), which represents the electrogenic sodium transport through Na+ channels, rose significantly from day 5, reached a peak on day 10, and entirely disappeared after weaning. The maximum rate of electrogenic, amiloride-sensitive sodium transport was 12.0 microEq/cm2 X h. The IscNa was suppressed by adrenalectomy and/or premature weaning but not by a mineralocorticoid antagonist, spironolactone. On the contrary, treatments which increase aldosterone levels in vivo (low-sodium diet, furosemide-induced natriuresis, high dietary intake of potassium) stimulated the IscNa. The effect of adrenalectomy increased during postnatal development. The sensitivity of IscNa to aldosterone was highest at the end of the weaning period. High-sodium diet, which causes a decrease in circulating aldosterone, was associated with a partial inhibition of IscNa (P less than 0.016). These data suggest that the distal colon of neonatal rats can transport sodium via an electrogenic, amiloride-sensitive mechanism and that adrenocortical hormones exert the main regulatory control of this pathway.
Electrogenic K+ secretion across the distal colon of young rats was investigated by measuring the sensitivity of the short-circuit current to Ba2+ added to the mucosal side of the tissue. Ba2+-sensitive short-circuit current (IBasc) was high during the suckling and weaning periods but very low in adult animals. Increasing the mucosal K+ concentration was accompanied by the inhibition of the serosa-to-mucosa IBasc and the induction of the mucosa-to-serosa IBasc. The IBasc was decreased by serosal omission of either Na+ or Cl- as well as by serosal addition of furosemide or ouabain. Mucosal omission of Na+ did not change IBasc. By increasing the plasma level of aldosterone (low-sodium diet) IBasc rose by 95% whereas treatment decreasing this level (high-sodium diet) reduced IBasc by 76%. Bilateral adrenalectomy lowered IBasc by 59% and treatment of adrenalectomized rats with deoxycorticosterone acetate prevented the reduction of IBasc. Tetraethylammonium and quinidine had similar effects on Isc as Ba2+. These data are consistent with the presence of a high level of K+ secretion in the distal colon of neonatal rats. This secretory pathway is electrogenic and independent of Na+ absorption. It appears to be mediated by the Na-K-ATPase as well as a furosemide-sensitive Na-Cl or Na-Cl-K cotransport on the basolateral side and by Ba2+-sensitive K+ conductive pathways on the mucosal side. The results suggest that this K+ secretion can be regulated by mineralocorticoids. The mineralocorticoids are necessary for "stimulated" K+ secretion but they are not essential for maintaining "basal" K+ secretion.
The functional heterogeneity of different segments of the rat large intestine was investigated by means of transepithelial potential difference (PD), short-circuit current (Isc) and transepithelial resistance (Rt) measurements in control rats and after deoxycorticosterone acetate (DOCA) pretreatment. Rt and PD were low in caecum and proximal colon but higher in the distal colon and rectum. Isc was highest in the distal colon, lower in the caecum, proximal colon, and rectum. None of the electrical properties was sensitive to amiloride in control conditions. DOCA increased PD and Isc in the caecum, distal colon and rectum but had no effect in the proximal colon. The increase of the Isc after DOCA in the distal colon and rectum was reached by induction of the amiloride-sensitive Isc associated with reduction of the amiloride-insensitive Isc. The effect of DOCA could be completely prevented by concurrent spironolactone treatment. The results suggest that the epithelia of the proximal parts of the large intestine are "leaky" whereas those of the distal colon and rectum are relatively "tight". It is concluded that there is a marked quantitative and qualitative segmental heterogeneity along the rat large intestine.
The influence of experimental neurosis due to repeated conflict situations on blood pressure was studied in male monkeys. All animals developed hypertension demonstrable in the conscious state but which disappeared under pentobarbital anaesthesia. Both in conscious and anaesthetized animals, the pulse pressure was in-elevated. The hypertension was accompanied by increased plasma volume to interstitial volume ratio, due to a decrease of the interstitial fluid compartment. The plasma renin concentration was not raised. It is suggested that chronic increase in blood pressure might be responsible for the decrease in compliance of large arteries (as evidenced by increased pulse pressure). This form of hypertension does not depend on the activity of the renin-angiotensin system.
Transport and electrical properties of the chick chorioallantoic membrane (CAM) were studied in order to find the osmoregulatory organ which helps to compensate the renal filtration-reabsorption disbalance of chick embryos. It could be shown that CAM resembles Na+ transporting epithelia in that active Na+ absorption is responsible for the potential difference and short circuit current, which could be abolished by ouabain on the ectodermal and amiloride on the endodermal side. The transepithelial conductance rose with increasing sodium concentration in accordance with the Michaelis-Menten kinetics. The allantoic sac thus plays a role similar to the toad urinary bladder despite the low potential difference and resistance which indicate that CAM is a leaky epithelium. CAM is therefore not only a respiratory but also an osmoregulatory organ.
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1. In rat kidney cortex, outer and inner medulla the development of activities of seven enzymes was investigated during postnatal ontogeny (10, 20, 30, 60 and 90 days of age). The enzymes were selected in such a manner, as to characterize most of the main metabolic pathways of energy supplying metabolism: hexokinase (glucose phosphorylation, HK), glycerol-3-phosphate dehydrogenase (glycerolphosphate metabolism or shunt, GPDH), triose phosphate dehydrogenase (glycolytic carbohydrate breakdown, TPDH), lactate dehydrogenase (lactate metabolism, LDH), citrate synthase (tricarboxylic acid cycle, aerobic metabolism, CS), malate NAD dehydrogenase (tricarboxylic acid cycle, intra-extra mitochondrial hydrogen transport, MDH) and 3-hydroxyacyl-CoA-dehydrogenase (fatty acid catabolism, HOADH). 2. The renal cortex already differs metabolically from the medullar structures on the 10th day of life. It displays a high activity of aerobic breakdown of both fatty acids and carbohydrates. Its metabolic capacity further increases up to the 30th day of life. 3. The outer medullar structure is not grossly different from the inner medulla on the 10th day of life. Further it differentiates into a highly aerobic tissue mainly able to utilize carbohydrates. It can, however, to some extent, also utilize fatty acids aerobically and produce lactate from carbohydrates anaerobically. 4. The inner medullar structure is best equipped to utilize carbohydrates by anaerobic glycolysis, forming lactate. This feature is already pronounced on the 10th day of life, its capacity increases to some extent during postnatal development, being highest between the 10th and the 60th day of life.
In salt-hypertensive monkeys, a decrease in plasma volume was found, inversely related to blood pressure level and not accompanied by a corresponding change in interstitial fluid volume.
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The O-specific polysaccharide obtained from Shigella dysenteriae type-2 lipopolysaccharide by mild acid hydrolysis consisted of N-acetylgalactosamine, N-acetylglucosamine, D-galactose, D-glucose, and O-acetyl group in the ratio of 2:1:1:1:1. A number of oligosaccharides were obtained by deamination of the N-deacetylated polysaccharide and by Smith degradation of the both native and O-deacetylated polysaccharides. The identification of oligosaccharides along with methylation analysis and chromic anhydride oxidation showed that the polysaccharide was built up of the repeating pentasaccharide units whose proposed structure is given below: (see article) Serological properties of Sh. dysenteriae O-specific polysaccharides are discussed.
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Drinking saline instead of water elevated the glomerular count in hypertrophied kidneys of rats uninephrectomized as adults. No changes occurred in glomerular concentration in kidney tissue indicating a more marked increase of other kidney structures. This procedure was ineffective in immature animals.